1. Field of the Invention
This invention relates to assays for detecting microbial infections in mammals by the detection of the action of enzymes produced by the microbes upon suitable substrates.
2. Description of the Background Art
The successful treatment of an infectious disease requires its prompt recognition and diagnosis. Currently, specific therapy of infectious diseases is largely limited to infections caused by bacteria and fungi. It is thus most important that bacterial or fungal infections be promptly recognized. Rapid diagnosis is especially important in newborns, immunocompromised children and patients undergoing cancer treatment in whom the rapid institution of appropriate chemotherapy is necessary to prevent a high rate of morbidity and mortality. However, currently available cultivation techniques are often not sufficiently rapid so that the diagnostic information is available to the physician at a time when a therapeutic decision must be made. This is especially true in the case of systemic fungal infections, which are often not diagnosed by cultivation techniques until long after the start of the clinical illness. While antigen detection systems such as counter-immunoelectrophoresis, radioimmunoassay and enzyme-linked immunosorbent assay can provide for rapid diagnosis of certain cases, they are limited to the detection of a single or small number of antigens. Immunological assays are not practical for the detection of antigens which have multiple antigenic types. Such assays are thus not useful for the diagnosis of febrile patients who might have an infection caused by any one of a large number of microorganisms. While microscopic techniques such as gram staining can provide valuable information in a short period of time, the sensitivity and scope of these techniques are limited and their results are subject to observer error. Also, available assays for bacterial endotoxins are not sufficiently sensitive to provide for a reliable diagnosis of systemic bacterial infection. In addition, currently available radiometric assays, which measure the generation of .sup.14 CO.sub.2 from .sup.14 C-glucose, require 16 to 24 hours to complete and often exhibit non-specific reactions since they measure a metabolic pathway common to both microbial and human cells. This is especially a problem in the testing of blood specimens from newborns and infants, where the increased metabolism of white cells makes the results of such assay systems difficult to interpret. In addition, these systems do not have the ability to detect fungal infections.